According to Erickson-Gini (2014), there is substantial evidence from the late Roman and early Byzantine residential quarter in Avdat that shows that a massive earthquake struck in the early 5th century CE ( Erickson-Gini 2010a:91–93). All structures east of the town wall were subsequently abandoned and quarried for reuse in the construction of the later Byzantine settlement. In the aftermath of this event, massive revetment walls were constructed along the southern side of the acropolis to stabilize heavily damaged masonry. In contrast, the late Byzantine citadel adjoining the temenos was built without such reinforcement, indicating that it was constructed after the earthquake. Erickson-Gini further observed that two churches within the temenos were built using a large number of early Roman ashlars and architectural elements that had originally belonged to the Obodas Temple, which was itself heavily damaged in the same event (Erickson-Gini 2014).

Numismatic and ceramic evidence from this destruction layer indicates that the dwellings in the late Roman and early Byzantine residential quarter were destroyed several decades after the 363 CE earthquake ( Erickson-Gini in Stern et al. 2008:1984–1985). Following this second event, the area was abandoned and many stones were robbed for reuse.

Additional archaeoseismic evidence was documented in Area A of the Roman–Byzantine Quarter, where Erickson-Gini (2022) reported fallen floor slabs—likely from an upper storey—and collapsed arches attributable to the same early 5th-century event. In the so-called “Dipinti cave” on the southern slope of the acropolis (Area D), a niche that originally functioned as a window was sealed and reinforced—likely in response to earthquake damage ( Erickson-Gini 2022). Further supporting evidence comes from Zion et al. (2022:30), who documented the destruction of quarters housing Roman soldiers east of and adjacent to the acropolis during the same seismic event.

The cumulative evidence points to the 419 CE Monaxius and Plinta earthquake as the cause of this widespread damage however, some scholars, such as Negev (1989), have argued for a broader time window that could extend into the late 5th century CE, suggesting that one or more events—including the hypothesized ~500 CE Negev Quake -may have also contributed to the observed destruction. Negev (1989) dated the causative earthquake to between "the end of the third century A.D., when the latest building in this quarter was constructed, and A.D. 541, when the Martyrium of St. Theodore was already being used as a burial ground."

Negev (1989) also described the archaeoseismic evidence. The entire length of the old southern Nabataean retaining wall at Oboda was displaced outward and had to be buttressed by a heavy slanting support wall. Severe damage also affected a massive Nabataean-period tower—likely the temple of Obodas—which had been incorporated into the citadel on the eastern half of the acropolis. The western and southern walls of this structure were particularly affected, requiring the construction of heavy taluses that blocked the original southern entrance and butressed the structure. Against this support the South Church was later built. Similar destruction was observed in adjacent buildings of the so-called Roman Quarter.